Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 Apr;114(8):1549–1556. doi: 10.1111/j.1476-5381.1995.tb14938.x

Mechanisms of bradykinin-induced contraction of the guinea-pig gallbladder in vitro.

D A Cabrini 1, A M Silva 1, J B Calixto 1
PMCID: PMC1510381  PMID: 7599922

Abstract

1. The mechanisms underlying bradykinin (BK)-mediated contractions in strips of guinea-pig gallbladder (GPG) were examined by use of selective bradykinin (BK) receptor agonists and antagonists. 2. Addition of BK and related kinins (0.1 pM-10 microM) after 2 h of equilibration of the preparation caused graded contractions characterized by two distinct phases: high affinity (0.1 pM-1 nM) and low affinity (3 nM-10 microM). The rank order of potency for the first phase (mean EC50, pM) was: BK (1.36) = Hyp3-BK (1.44) = Lys-BK (1.54) > Tyr8-BK (2.72) > Met-Lys-BK (4.30). The rank order of potency for the second phase (mean EC50, nM, at concentration producing 50% of the contraction caused by 80 mM KCl) was: Hyp3-BK (8.95) > Met-Lys-BK (12.78) > Tyr8-BK (33.75) > Lys-BK caused by 80 mM KCl) was: Hyp3-BK (8.95) > Met-Lys-BK (12.78) > Tyr8-BK (33.75) > Lys-BK (60.92) > BK (77.35). The contractile responses (g of tension) to 3 microM of BK (the highest concentration tested) were: Hyp3-BK, 1.76 +/- 0.09; BK, 1.65 +/- 0.12; Lys-BK, 1.45 +/- 0.13; Tyr8-BK, 1.36 +/- 0.15 and Met-Lys-BK, 1.36 +/- 0.15. The selective B1 agonist, des-Arg9-BK, caused only a weak contraction with maximal response (0.21 +/- 0.05 g), which corresponded to approximately 10% of that induced by BK.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1549

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baird A. W., Margolius H. S. Bradykinin stimulates electrogenic bicarbonate secretion by the guinea pig gallbladder. J Pharmacol Exp Ther. 1989 Jan;248(1):268–272. [PubMed] [Google Scholar]
  2. Bathon J. M., Proud D. Bradykinin antagonists. Annu Rev Pharmacol Toxicol. 1991;31:129–162. doi: 10.1146/annurev.pa.31.040191.001021. [DOI] [PubMed] [Google Scholar]
  3. Bhoola K. D., Figueroa C. D., Worthy K. Bioregulation of kinins: kallikreins, kininogens, and kininases. Pharmacol Rev. 1992 Mar;44(1):1–80. [PubMed] [Google Scholar]
  4. Bramley A. M., Samhoun M. N., Piper P. J. The role of the epithelium in modulating the responses of guinea-pig trachea induced by bradykinin in vitro. Br J Pharmacol. 1990 Apr;99(4):762–766. doi: 10.1111/j.1476-5381.1990.tb13003.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burch R. M., Farmer S. G., Steranka L. R. Bradykinin receptor antagonists. Med Res Rev. 1990 Apr-Jun;10(2):237–269. doi: 10.1002/med.2610100204. [DOI] [PubMed] [Google Scholar]
  6. Calixto J. B., Medeiros Y. S. Characterization of bradykinin mediating pertussis toxin-insensitive biphasic response in circular muscle of the isolated guinea pig ileum. J Pharmacol Exp Ther. 1991 Nov;259(2):659–665. [PubMed] [Google Scholar]
  7. Campos A. H., Calixto J. B. Mechanisms involved in the contractile responses of kinins in rat portal vein rings: mediation by B1 and B2 receptors. J Pharmacol Exp Ther. 1994 Feb;268(2):902–909. [PubMed] [Google Scholar]
  8. Deshpande Y. G., Kaminski D. L. Identification and quantitation by radioimmunoassay of prostaglandin F compounds in bile. Prostaglandins. 1980 Aug;20(2):367–372. doi: 10.1016/s0090-6980(80)80053-0. [DOI] [PubMed] [Google Scholar]
  9. Falcone R. C., Hubbs S. J., Vanderloo J. D., Prosser J. C., Little J., Gomes B., Aharony D., Krell R. D. Characterization of bradykinin receptors in guinea pig gall bladder. J Pharmacol Exp Ther. 1993 Sep;266(3):1291–1299. [PubMed] [Google Scholar]
  10. Freedman S. M., Wallace J. L., Shaffer E. A. Characterization of leukotriene-induced contraction of the guinea-pig gallbladder in vitro. Can J Physiol Pharmacol. 1993 Feb;71(2):145–150. doi: 10.1139/y93-020. [DOI] [PubMed] [Google Scholar]
  11. Girard Y., Yoakim-Rancourt C., Hamel P., Gillard J. W., Guindon Y., Letts G., Evans J., Léveillé C., Ethier D., Lord A. Tetrahydrocarbazol-1-acetic acids: new class of thromboxane receptor antagonists. Prog Clin Biol Res. 1989;301:585–589. [PubMed] [Google Scholar]
  12. Hall J. M. Bradykinin receptors: pharmacological properties and biological roles. Pharmacol Ther. 1992 Nov;56(2):131–190. doi: 10.1016/0163-7258(92)90016-s. [DOI] [PubMed] [Google Scholar]
  13. Hall R. A., Gillard J., Guindon Y., Letts G., Champion E., Ethier D., Evans J., Ford-Hutchinson A. W., Fortin R., Jones T. R. Pharmacology of L-655,240 (3-[1-(4-chlorobenzyl)-5-fluoro-3-methyl-indol-2-yl]2,2-dimethylpro pan oic acid); a potent, selective thromboxane/prostaglandin endoperoxide antagonist. Eur J Pharmacol. 1987 Mar 17;135(2):193–201. doi: 10.1016/0014-2999(87)90611-x. [DOI] [PubMed] [Google Scholar]
  14. Hidaka H., Kobayashi R. Pharmacology of protein kinase inhibitors. Annu Rev Pharmacol Toxicol. 1992;32:377–397. doi: 10.1146/annurev.pa.32.040192.002113. [DOI] [PubMed] [Google Scholar]
  15. Jenden D. J., Fairhurst A. S. The pharmacology of ryanodine. Pharmacol Rev. 1969 Mar;21(1):1–25. [PubMed] [Google Scholar]
  16. Jones T. R., Zamboni R., Belley M., Champion E., Charette L., Ford-Hutchinson A. W., Frenette R., Gauthier J. Y., Leger S., Masson P. Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist. Can J Physiol Pharmacol. 1989 Jan;67(1):17–28. doi: 10.1139/y89-004. [DOI] [PubMed] [Google Scholar]
  17. Kaminski D. L. Arachidonic acid metabolites in hepatobiliary physiology and disease. Gastroenterology. 1989 Sep;97(3):781–792. doi: 10.1016/0016-5085(89)90655-0. [DOI] [PubMed] [Google Scholar]
  18. Kaminski D. L., Deshpande Y. G., Qualy J., Thomas L. A. The role of prostaglandins in feline experimental cholecystitis. Surgery. 1985 Oct;98(4):760–768. [PubMed] [Google Scholar]
  19. Marceau F., Lussier A., Regoli D., Giroud J. P. Pharmacology of kinins: their relevance to tissue injury and inflammation. Gen Pharmacol. 1983;14(2):209–229. doi: 10.1016/0306-3623(83)90001-0. [DOI] [PubMed] [Google Scholar]
  20. Meissner G. Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. J Biol Chem. 1986 May 15;261(14):6300–6306. [PubMed] [Google Scholar]
  21. Myers S. I., Bartula L. Human cholecystitis is associated with increased gallbladder prostaglandin I2 and prostaglandin E2 synthesis. Hepatology. 1992 Nov;16(5):1176–1179. [PubMed] [Google Scholar]
  22. Proud D., Kaplan A. P. Kinin formation: mechanisms and role in inflammatory disorders. Annu Rev Immunol. 1988;6:49–83. doi: 10.1146/annurev.iy.06.040188.000405. [DOI] [PubMed] [Google Scholar]
  23. Randall M. J., Parry M. J., Hawkeswood E., Cross P. E., Dickinson R. P. UK-37, 248, a novel, selective thromboxane synthetase inhibitor with platelet anti-aggregatory and anti-thrombotic activity. Thromb Res. 1981 Jul 1;23(1-2):145–162. doi: 10.1016/0049-3848(81)90247-4. [DOI] [PubMed] [Google Scholar]
  24. Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
  25. Schlemper V., Calixto J. B. Nitric oxide pathway-mediated relaxant effect of bradykinin in the guinea-pig isolated trachea. Br J Pharmacol. 1994 Jan;111(1):83–88. doi: 10.1111/j.1476-5381.1994.tb14027.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Thornell E., Jansson R., Svanvik J. Indomethacin intravenously--a new way for effective relief of biliary pain: a double-blind study in man. Surgery. 1981 Sep;90(3):468–472. [PubMed] [Google Scholar]
  27. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES